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Several new mouse models of fast amyloid deposition have been generated with compound mutations, but how these affect high\u2010level cognitive function is still not fully understood. Four cohorts of a second\u2010generation amyloid precursor protein knock\u2010in mouse model,\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>NL\u2010G\u2010F\/NL\u2010G\u2010F<\/jats:sup>\n                    , which develops aggressive amyloidopathy, were compared with two different control groups that do not produce plaques (\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>NL\/NL<\/jats:sup>\n                    and wildtype littermates), on touchscreen\u2010based tests of learning and cognitive flexibility.\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>NL\u2010G\u2010F\/NL\u2010G\u2010F<\/jats:sup>\n                    mice learned to discriminate between two visual stimuli during the pairwise visual discrimination (PVD) task but were impaired when the reward contingencies were reversed (the PVR task). Analyses of the correction trials indicated perseverative behavior. One cohort was further tested on the touchscreen Extinction test, which isolates the ability to withhold responding to a previously rewarded stimulus. The\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>NL\u2010G\u2010F\/NL\u2010G\u2010F<\/jats:sup>\n                    mice extinguished their responding no differently than the\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>NL\/NL<\/jats:sup>\n                    control group. These results indicate that compound mutations in\n                    <jats:italic>App<\/jats:italic>\n                    driving fast accumulation of plaques in this mouse model impair cognitive flexibility and may serve as a preclinical target for putative therapeutic drugs.\n                  <\/jats:p>","DOI":"10.1111\/gbb.70024","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:39:24Z","timestamp":1748867964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impaired Cognitive Flexibility With Preserved Learning in an Amyloid Precursor Protein Knock\u2010In Mouse Model of Amyloidopathy"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2412-306X","authenticated-orcid":false,"given":"Julie R.","family":"Dumont","sequence":"first","affiliation":[{"name":"BrainsCAN, Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-1446","authenticated-orcid":false,"given":"Paul A. 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